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Correlation of Non-tumoral Liver Dose with Treatment-Related Adverse Events in Patients with Hepatocellular Carcinoma Treated with Glass-Based Yttrium-90 Radioembolization

  • Clinical Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the relationship between non-tumor liver (NTL) dose and adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with glass-based Yttrium-90 radioembolization (Y90-RE).

Materials and Methods

A retrospective analysis of patients with HCC treated with Y90-RE between 2013 and 2018 was performed. Baseline characteristics including demographics and Y90-RE treatment approach were captured. Common Terminology Criteria for Adverse Events v5 was assessed at months 3 and 6 post-treatment. Using voxel-based dosimetry with MIM Software V. 6.9, dose-volume histograms of treated area of liver were created. Receiver operator characteristic curve was used to determine NTL dose threshold predicting AEs. Multivariate analysis was used to determine independent clinical factors of predicting severe AEs. Chi-square analysis was used to compare proportions.

Results

Two hundred and twenty-nine consecutive patients (115(50.2%) lobar and 114(49.8%) segmental) were included. At 3 months, there was a lower rate of any grade AE (55(46%) segmental and 36(31%) lobar, p = 0.009) and increased rate of severe AEs for lobar compared to segmental (2(2%) segmental and 9(8%) lobar, p = 0.029). At 6 months, severe AEs were greater for lobar than segmental (1(1%) segmental vs 10(9%) lobar, p = 0.005). For lobar Y90-RE, mean NTL dose of 112 Gy predicted severe AE (89% sensitivity and 91% specificity (AUC = 0.95, p =  < 0.0001) at 3 and 6 months. For the segmental group, no significant association was found between NTL dose and severe treatment-related AE at 3 and 6 months.

Conclusion

In patients with HCC undergoing glass-based lobar Y90-RE, NTL dose of > 112 Gy is associated with severe treatment-related AEs at 3–6 months.

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References

  1. Garin E, et al. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(1):17–29.

    Article  Google Scholar 

  2. Shah RM, et al. Prognostic factors of unresectable hepatocellular carcinoma treated with yttrium-90 radioembolization: results from a large cohort over 13 years at a single center. J Gastrointest Oncol. 2021;12(4):1718–31.

    Article  Google Scholar 

  3. Moreno-Luna LE, et al. Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2013;36(3):714–23.

    Article  Google Scholar 

  4. Lance C, et al. Comparative analysis of the safety and efficacy of transcatheter arterial chemoembolization and yttrium-90 radioembolization in patients with unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2011;22(12):1697–705.

    Article  Google Scholar 

  5. Hilgard P, et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology. 2010;52(5):1741–9.

    Article  CAS  Google Scholar 

  6. Salem R, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497-507.e2.

    Article  Google Scholar 

  7. El Fouly A, et al. In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int. 2015;35(2):627–35.

    Article  Google Scholar 

  8. Gabr A, et al. Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants. Eur J Nucl Med Mol Imaging. 2021;48(2):580–3.

    Article  CAS  Google Scholar 

  9. Levillain H, et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging. 2021;48(5):1570–84.

    Article  Google Scholar 

  10. Camacho JC, et al. (90)Y Radioembolization: multimodality imaging pattern approach with angiographic correlation for optimized target therapy delivery. Radiographics. 2015;35(5):1602–18.

    Article  Google Scholar 

  11. Package Insert: TheraSphere Yttrium-90 Glass Microspheres. [cited 6 February 2022]; https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwi_h-qxxuz1AhVkjYkEHSDnBocQFnoECAMQAQ&url=https%3A%2F%2Fwww.accessdata.fda.gov%2Fcdrh_docs%2Fpdf%2Fh980006c.pdf&usg=AOvVaw3DTs9oqnqZ43-boZ5FwCzu.

  12. Villalobos A, et al. Tumor-to-normal ratio relationship between planning technetium-99 macroaggregated albumin and posttherapy Yttrium-90 Bremsstrahlung SPECT/CT. J Vasc Interv Radiol. 2021;32(5):752–60.

    Article  Google Scholar 

  13. Bolch WE, et al. MIRD pamphlet No 17: the dosimetry of nonuniform activity distributions–radionuclide S values at the voxel level medical internal radiation dose committee. J Nucl Med. 1999;40(1):11s–36s.

    CAS  Google Scholar 

  14. Bolch WE, et al. MIRD pamphlet No 21: a generalized schema for radiopharmaceutical dosimetry–standardization of nomenclature. J Nucl Med. 2009;50(3):477–84.

    Article  CAS  Google Scholar 

  15. Elsayed M, et al. Comparison of Tc-99m MAA planar versus SPECT/CT imaging for lung shunt fraction evaluation prior to Y-90 radioembolization: are we overestimating lung shunt fraction? Cardiovasc Intervent Radiol. 2021;44(2):254–60.

    Article  Google Scholar 

  16. Knešaurek K. An estimate of (90)Y dosimetry for bremsstrahlung SPECT/CT imaging in liver therapy with (90)Y microspheres. Eur J Radiol. 2021;139: 109698.

    Article  Google Scholar 

  17. Potrebko PS, et al. SPECT/CT image-based dosimetry for Yttrium-90 radionuclide therapy: application to treatment response. J Appl Clin Med Phys. 2018;19(5):435–43.

    Article  Google Scholar 

  18. Nelson A, Swallen A, Dewaraja Y. Evaluation of a voxel-based yttrium-90 (Y-90) dose calculation method for Bremsstrahlung SPECT using a liver phantom. J Nucl Med. 2016;57(supplement 2):306–306.

    Google Scholar 

  19. Skanjeti A, et al. Selective internal radiation therapy of hepatic tumors: morphologic and functional imaging for voxel-based computer-aided dosimetry. Biomed Pharmacother. 2020;132: 110865.

    Article  CAS  Google Scholar 

  20. Sankhla T, et al. Role of resin microsphere y90 dosimetry in predicting objective tumor response, survival and treatment related toxicity in surgically unresectable colorectal liver metastasis: a retrospective single institution study. Cancers (Basel). 2021;13(19):4908.

    Article  CAS  Google Scholar 

  21. Program, N.C.T.E. Common terminology criteria for adverse events (CTCAE). 2020 [cited 6 February 2022]; https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.

  22. Oken MM, et al. Toxicity and response criteria of the Eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649–55.

    Article  CAS  Google Scholar 

  23. Garin E, et al. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept. Eur J Nucl Med Mol Imaging. 2013;40(7):1057–68.

    Article  CAS  Google Scholar 

  24. Chiesa C, et al. Radioembolization of hepatocarcinoma with 90Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology. Eur J Nucl Med Mol Imaging. 2015;42(11):1718–38.

    Article  CAS  Google Scholar 

  25. Garin E, et al. High impact of macroaggregated albumin-based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with (90) Y-loaded glass microsphere radioembolization. Liver Int official J Int Assoc Study Liver. 2017;37(1):101–10.

    CAS  Google Scholar 

  26. Chan KT, et al. Hepatotoxic dose thresholds by positron-emission tomography after yttrium-90 radioembolization of liver tumors: a prospective single-arm observational study. Cardiovasc Intervent Radiol. 2018;41(9):1363–72.

    Article  Google Scholar 

  27. South CD, et al. Yttrium-90 microsphere induced gastrointestinal tract ulceration. World J Surg Oncol. 2008;6:93.

    Article  Google Scholar 

  28. Riaz A, et al. Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J Vasc Interv Radiol. 2009;20(9):1121–30.

    Article  Google Scholar 

  29. Lam M et al. A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study. Eur J Nucl Med Mol Imaging. 2022;49(10):3340–52.

    Article  CAS  Google Scholar 

  30. Padia SA, et al. Comparison of positron emission tomography and bremsstrahlung imaging to detect particle distribution in patients undergoing yttrium-90 radioembolization for large hepatocellular carcinomas or associated portal vein thrombosis. J Vasc Interv Radiol. 2013;24(8):1147–53.

    Article  Google Scholar 

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Funding

This article was funded by Sirtex Medical and Boston Scientific Corporation.

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Authors and Affiliations

  1. Division of Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Linzi A. Webster, Alex Villalobos, Bernard Cheng, Bill S. Majdalany, Zachary L. Bercu, Mircea M. Cristescu, Yoram Baum, Mohammed F. Loya & Nima Kokabi

  2. Office of Epidemiology, Dekalb Country Board of Health, Atlanta, GA, USA

    Minzhi Xing

  3. Department of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA

    David Brandon & David Schuster

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  1. Linzi A. Webster
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  2. Alex Villalobos
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Corresponding author

Correspondence to Linzi A. Webster.

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Conflict of interest

Nima Kokabi, MD, receives research support from SIRtex Medical. Nima Kokabi, MD receives educational grant from Boston Scientific. Bill S. Majdalany, MD, serves on the scientific advisory board of Balt Medical. The remaining authors have no conflicts of interests to disclose.

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This study was IRB-approved, and, due to the retrospective nature of this work, no formal consent was required.

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Webster, L.A., Villalobos, A., Cheng, B. et al. Correlation of Non-tumoral Liver Dose with Treatment-Related Adverse Events in Patients with Hepatocellular Carcinoma Treated with Glass-Based Yttrium-90 Radioembolization. Cardiovasc Intervent Radiol 46, 60–68 (2023). https://doi.org/10.1007/s00270-022-03314-9

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